Scott, S.D., Marples, B., Hendry, J.H., Lashford, L.S., Embleton, M.J., Hunter, R.D., Howell, A. and Margison, G.P. (2000) A radiation-controlled molecular switch for use in gene therapy of cancer. Gene Therapy, 7 (13). pp. 1121-1125. (doi:https://doi.org/10.1038/sj.gt.3301223)

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Abstract

Ionising radiation induces the expression of a number of radiation-responsive genes and there is current interest in exploiting this to regulate the expression of exogenous therapeutic genes in gene therapy strategies for cancer. However, the radiation-responsive promoters used in these approaches are often associated with low and transient levels of therapeutic gene expression. We describe here a novel radiation-triggered molecular switching device based on promoter elements from the radiation-responsive Egr-1 gene and the cre-LoxP site-specific recombination system of the P1 bacteriophage. Using this system, a single, minimally toxic dose of radiation induced cre-mediated excision of a lox-P flanked stop cassette in a silenced expression vector and this resulted in amplified levels of CMV-promoter-driven expression of the exogenous tumour-sensitising gene, HSV-tk. This strategy could be used in combination with targeted delivery and tumour-specific promoters to elicit the tumour-targeted and prolonged expression of a variety of tumour-sensitising genes and provide an unprecedented level of control and tumour selectivity.

Item Type:	Article
Uncontrolled Keywords:	radiotherapy, radiation-responsive elements, molecular switch, CRE recombinase, HSVtk, ganciclovir
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) T Technology > TP Chemical technology
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science > Medway School of Pharmacy
Related URLs:	Publisher Organisation
Last Modified:	01 Nov 2016 11:14
URI:	http://gala.gre.ac.uk/id/eprint/8478

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